Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Pozo, K; Hillmann, A; Augustyn, A; Plattner, F; Hai, T; Singh, T; Ramezani, S; Sun, X; Pfragner, R; Minna, JD; Cote, GJ; Chen, H; Bibb, JA; Nwariaku, FE.
Differential expression of cell cycle regulators in CDK5-dependent medullary thyroid carcinoma tumorigenesis.
Oncotarget. 2015; 6(14):12080-12093
Doi: 10.18632/oncotarget.3813
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- Co-authors Med Uni Graz
- Pfragner Roswitha
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- Abstract:
- Medullary thyroid carcinoma (MTC) is a neuroendocrine cancer of thyroid C-cells, for which few treatment options are available. We have recently reported a role for cyclin-dependent kinase 5 (CDK5) in MTC pathogenesis. We have generated a mouse model, in which MTC proliferation is induced upon conditional overexpression of the CDK5 activator, p25, in C-cells, and arrested by interrupting p25 overexpression. Here, we identify genes and proteins that are differentially expressed in proliferating versus arrested benign mouse MTC. We find that downstream target genes of the tumor suppressor, retinoblastoma protein, including genes encoding cell cycle regulators such as CDKs, cyclins and CDK inhibitors, are significantly upregulated in malignant mouse tumors in a CDK5-dependent manner. Reducing CDK5 activity in human MTC cells down-regulated these cell cycle regulators suggesting that CDK5 activity is critical for cell cycle progression and MTC proliferation. Finally, the same set of cell cycle proteins was consistently overexpressed in human sporadic MTC but not in hereditary MTC. Together these findings suggest that aberrant CDK5 activity precedes cell cycle initiation and thus may function as a tumor-promoting factor facilitating cell cycle protein expression in MTC. Targeting aberrant CDK5 or its downstream effectors may be a strategy to halt MTC tumorigenesis.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Carcinogenesis - genetics
- Carcinoma, Medullary - congenital
- Carcinoma, Medullary - genetics
- Carcinoma, Medullary - metabolism
- Cell Cycle - genetics
- Cell Line, Tumor -
- Cyclin-Dependent Kinase 5 - genetics
- Gene Expression -
- Humans -
- Mice -
- Multiple Endocrine Neoplasia Type 2a - genetics
- Multiple Endocrine Neoplasia Type 2a - metabolism
- Thyroid Neoplasms - genetics
- Thyroid Neoplasms - metabolism
- Find related publications in this database (Keywords)
- Cdk5
- retinoblastoma protein
- neuroendocrine
- medullary thyroid carcinoma
- cell cycle